To the Editor: In their clinical trial, Dr Wu and colleagues1 reported clinically significant benefits of metformin and lifestyle interventions in reducing antipsychotic-induced weight gain in patients with schizophrenia. In addition to the mechanisms for this finding that were considered by the authors, the effect of these interventions on levels of insulinlike growth factor 1 (IGF-1) deserves further exploration. Although an animal study suggests that exercise may increase circulating IGF-1 levels,2 a small study in healthy men suggests that metformin decreases IGF-1.3 Although exercise and metformin resulted in similar short-term benefits on antipsychotic-induced weight gain in the study by Wu et al, their long-term effects on IGF-1 might be important to consider in these patients.